July 20, 1955
3869
THIOLS WITH N-BENZYLIDENEANILINE
and the resulting mixture extracted well with chloroform. After drying over anhydrous sodium sulfate and filtering from the drying agent, the chloroform extract was saturated with gaseous hydrogen chloride. The hydrochloride was collected on a suction filter and recrystallized from a mixture
of water and ethanol. The yield was 0.27 g. (40%). The salt did not melt below 250'. Anal. Calcd. for ClaH21CINz04S: S , 9.20. Found: S, 9.36. LEXINGTON, KENTUCKY
[CONTRIBUTION FROM THE FULMER CHEMICAL LABORATORY, STATE COLLEGE
OF
WASHINGTON]
Schiff Bases and Related Substances. 11. Reactions of Thiols with N-Benzylideneaniline and N-Benzylideneanthranilic Acid BY GARDNER W. STACY,RICHARD I. DAYAND RICHARD J. M O R A T H ~ RECEIVEDFEBRUARY 17, 1955
No substituent effect has been observed in the addition of thiols to m- and p-benzylideneaminohenzoic acids or m- and pbenzylideneaminoacetophenones. Under appropriate conditions, N-benzylideneaniline (111) has been found to form a d dition products with thiols as readily as N-benzylideneanthranilic acid ( I ) . Schiff base-thiol adducts are decomposed readily by dilute sodium hydroxide solution to yield constituent thiols and Schiff bases. Reduction of the p-toluenethiol adduct of N-benzylideneaniline (VI) occurs as readily as direct reduction of N-benzylideneaniline (111) with p-toluenethiol. Cleavage of Schiff bases by thiols in the presence of small amounts of water has been observed to yield corresponding amines and mercaptals.
I n a recent publication' from this Laboratory, hence adduct formation might be expected to it was demonstrated that N-benzylideneanthranilic occur readily. The same electron displacement, of acid (I) would form crystalline adducts (11) with a course, would not obtain in the case of meta isovariety of thiols. Earlier, Gilman and Dickey3 mers, and therefore i t might be thought that these had investigated the possibility of conjugate, would form adducts less readily or not a t all, as also would be the case with the unsubstituted C~H~CH=?JC~HICOOH-O $- RSH + Schiff base (III).6 I Such considerations were studied relative to the C&IKCH-NHCBHEOOH-O m- and p-benzylideneaminobenzoic acids (VII) I SR I1 and the m- and p-benzylideneaminoacetophenones nuclear addition of p-toluenethiol to N-benzyli- (VIII). However, as indicated by the yields deneaniline (111). They observed no addition (Table I), there was no indication that meta isoproducts, however, but instead found that I11 was , - pP1 ; ( ~ R ~ S H----f reduced to N-benzylaniline (IV). More recently, G H ~ C H = some examples of reduction of conjugated azoWI, R' = COOH methine systems have been r e p ~ r t e d . ~ VIII, R 1 = COCHa CaHsCH-.l.Hc>R1
+
_ .
__
I
SRP
c
2 ~-CHBCBHSH
IX
p-CH8C6Hdv1
caHbcH2NHcsH~f ( ~ - C H ~ C ~ H I S ) ~ 1v V
Because the Schiff bases I and I11 had been observed to react differently with thiols, i t was of obvious interest to study the different factors involved in the two cases. Initially, we wished to investigate the possibility of a substituent effect as a basis for adduct formation. An electronattracting substituent (as in the case of the carboxyl group in I) ortho or para to the Schiff base nitrogen might be expected to enhance the polarization of the carbon-nitrogen double bond, and (1) Presented in part before t h e Division of Organic Chemistry a t the 125th Meeting of the American Chemical Society, Kansas City, Mo., March 24, 1954, and in p a r t before the Montana Section of the American Chemical Society, Missoula, Mont., M a y , 1953. Paper I , G. W. Stacy and R . J. Morath, THIS JOURNAL, 74, 3885 (1952). (2) Abstracted from theses submitted by Richard I. Day and Richard J . Morath in partial fulfillment of the requirements for degrees of Master of Science and Doctor of Philosophy, respectively, State College of Washington, February, 1955, 1954. (3) H. Gilman and J. B. Dickey, THISJOURNAL, 61, 4573 (1930). (4) H. Gilman, J . L. Towle and R . K. Ingham, i b i d . , 76, 2920 (1954).
mers underwent adduct formation any less readily than para isomers. And certainly there were no striking differences in reactivity, as had been observed with the isomeric nitrostyrenes6 The above results suggested that the difference in the reactions that had been observed when I and I11 were treated with thiols must be due to differences in conditions under which the reactions had been carried out. Gilman and Dickey3 had run their reduction (111 IV) in refluxing pxylene with a threefold excess of thiol, whereas our additions (I + I1 and VII, VI11 + IX) were carried out equally well a t room temperature or in refluxing benzene with one to two equivalents of thiol. Therefore, the formation of adducts of Nbenzylideneaniline (111) was attempted employing the conditions that had led to addition in our previous experience. And, indeed, it was found that adducts of I11 were obtained in excellent yield (Table I). On the other hand, when the conditions that Gilman and Dickey3 had reported were ein( 5 ) Systems of comparative interest involve substituted styrenes. Recently, it has been reported t h a t 0- or P-nitrostyrenes will add active methylene compounds in the presence of sodium alkoxide, whereas mnitrostyrene and styrene itself will n o t ; W. J . Dale and C. W. Strobel, ibid., 76. 6172 (1954).
GAKDNER M:. STACY, RICHARD I. DAYAND RICHARD J. MORATH
3870
Vol. 77
TABLE I SCHIFF BASE-THIOL ADDUCTS (IX) J i2
I
-cr so extracted was removed by distil1:itioii; t i o IIIWc:iptal SI was isolated from the oily rcsiduc. The ether filtrates ( C ) from above wcrc cutr:t ,570 sodium hydroxide solution; when tile cxtr acidified with dilute hydrochloric acid. a gun After ether was added to the mixture, sonic of tlic gum diisolved leaving crystalline material ( D ) in the ;Iqucou\ p1i;isi.. The ether phase was dried, a n d then a stream of anhydrous hydrogen chloride was introduced t o give niorc cr!,stallilIc material (E). The combined crystalline materials ( I ) , JL in addition to other 5mall fractions of similar nxrtcrial t h , t t werc isolated from this reaction mixture appcarctl t o 1): the Iiydrochloride of nr-benzylaminobenzoic acid. tlic :tritiriI x i t c d reduction product; total yield 2.13 g . ( 3 2 % ) . I\ sample of In-henzylaminobenzoic acid was obt,iincd rroiii w m e relatively pure hydrochloride. Thc IiytIroc!ilorirl~ was dissolved in dilute sodium hydroxide solutioti, litltl til(, pH adjusted to 5.5 with dilute hydrochloric acid. TIICrc'sulting solution was then extractcd with foiir por ether and, after the combined extracts had Ijecii 111 in the usual manner, a product melting a t 10s -1 1 1 ' tained. This was recrystallized once from a m i x t u r e of I ml. of benzene and 3 ml. of petroleum ether a n d ~ ! I ( . I I trvic~ from %50% ethanol, m.p. 114-115".~7 Because of difficulties in isolating thc :i.iiinn :icitl i l l a pure condition, a sample of hydrochloritlc MYIY corivcrtctl 10 N-acetyl-m-benzylaminobenzoic acid. Iviirining tlic mixture on a steam-bath, a 0.200-g. sample of h>.tlroc!llorirlc was dissolved in 30 ml. of 107, sodium :tcct;tte solution. Tltc mixture w a s cooled in an ice-hath, and 3 nil. of acc!ic :tilhydride was added w i t h :Igitation. Almost iinincdi;ttel?. tile Eolution became turbid, and :til oil formctl. T l i c colt1 inistiire was niade strongly acidic with ! i > tlrocliloi-ic :wid, a n d tlicn it \ u s cxtracted w i t h ur p n r t i o n 5 of vtilcr.. 1 hc comhiric,tl extriicts \vt'rc procc 1 in t l i c i i i i i : i I 1 t 1 . i 1 1 1 i ( ' r ;iritl t i l e rcsitlur 1 ~ x 5tli\.iilvcd ill i v i i r ;iiiil 1 w c L t [ , ( l \ v i i J I O;
T 3 ~ r
,.
Soritc;
yieltl O.i)!l:; g..
t i i t c t i o r t ha\c.tl
oii
k\ii\
itlilc.
1/11
iii.11.
I:;() i : j l ".
Iiiit-c
:iext\!
'l'li(
v \ t c 1 1 1o i w -
ilvii\,tti\i
\\,I\
w . r > ~ [ ; i l I i z wIl I \ ~ < T I I I ) , I I Ci,,Il, , \ O '
I.:',?,.
io111~1 ; t1
C ' , ,-I
.->,211. l ~ o l i l l d : c . 7 l . ( i 2 ; 1 1 , :.x; s . .i. ( h ) N-Benzylideneanthranilic Acid f I ) . I ~ ~ ~ ~ i ~ r t i ~ ~ t l ~ ~ i ~ I \ v a s cmploved i n t h i s cypi>rimritt r,itlicr t ! l : i t t p - ~ o l i t c i l ( ~ ~ l i i o l ilfter the p-xyleite had been removed by iiistillatlot~.t l i l ' residue mas taken up in 200 ml. of ethcr, which IWS CYtracted with four portions of 10% sodium bicarhonatc solution. The combined extracts then mere acidified with tlilutr, hydrochloric acid, and the resulting prcripitatc was scparated to give the crude reduction product, S-bcnzyl:tnthranilic acid; yield O.62 g . , m.1). 151-167'. 1iecryst:tlliz:ttion from chloroform afforded a pure product, 0.42 g., 1n.p.
174.5-175". The ether phase from the ahove scparatioii \\-as then cxtracted with several portions of 1070sodium hydroxide solution. A crystallinc material, which \vas diicovcrcd in the interphase during this scparatiori, proved to be the sodium salt of some adrlitioiial reduction p r o t i w t . which upon acidification gave 0.34 g., m , p . 172~-173". T l ~ c extent of reduction wi'iis 1 3 % as haseti on the total a:noiint of rccr!.stallized product, 11.75 g., 1n.p. 174 -17;i0."
Acknowledgment.--R. J . 11, wishes to express appreciation for a predoctoral fellowship from the National Institutes of Health, United States Public Health Seri7ice, during the tenure of I 171 G. Lockemann and H . Rein, r h r m . Ber., 80, ,485 ( l n i 7 ) . r e ported m p . ' 1~1 5 O , 110'. f IS) The reported melting i m i n t for S-henz?.lanthrnnilic acid i > l i d ' (ref, 17).
whic!i a part u i tliis work was carried o u t . 'I'his investigation also was supported in part by a
grarit frolu the Naliolial St*iellc.e l;(tiiliilatioli PULLMAN, WASHINGTON
[CONTRIBUTION PROM DEPARTMENT O F BIOCHEMISTRY, UNIVERSITY OF
Studies on Thiols, I.
\~ASHINGTON]
Oxidation of Thiol Groups by 2,6-Dichlorophenol Indophenol' BY I
